The present invention relates to a roller bottle for cell growth and production, and more particularly, concerns a device for scraping the grown or cultured cells from the internal surface of the roller bottle in order to achieve enhanced harvesting of cells so grown.
Containers which are used in the laboratory in like situations for culturing of cells are commonly known as "roller bottles." These roller bottles are generally cylindrically shaped and are adapted to rotate about their axes. The interior surfaces of such roller bottles are for providing active surfaces for cells. A liquid growth medium is introduced into the roller bottle. The rotating movement of the bottle keeps the internal surfaces wetted with the liquid medium, thereby encouraging the growth of cells. Rotating rollers in an appropriate apparatus are employed to rotate these rollers. Usually, the roller bottle apparatus is adapted to be placed inside an incubator or incubating room to control the temperature of cell growth inside the roller bottles.
It is desirable to grow large amounts of cells, mostly for cell by-products, such as pharmaceutical substances that are secreted by cells; for example insulin, interferon, urokinase or viral vaccines. Standard roller bottles have been successful in increasing the yield of cell growth in as much as the entire inside peripheral surface area can be utilized for cell culturing.
In conceiving ways to increase the yield of growing cells in roller bottles, there are substantial constraints which have to be considered in suggesting improvements. In particular, roller bottle rotation devices are widely used in standard sizes and incubators. These devices are in place in many laboratories and are designed to accept roller bottles of a specific size and shape. Thus, to replace these would be expensive and cause substantial lack of standardization throughout the laboratory field. Thus, the outside configuration or diameter of roller bottles is generally not one of the parameters which is changed to improve the yield of cells grown in roller bottles. Accordingly, improvements in roller bottles for increasing cell growth, for practical purposes, is limited to modifications of interior surfaces of the roller bottle, and/or improvements in harvesting the cells once they are grown.
Various approches have been used in order to increase the surface area internally of roller bottles. One approach is to increase the amount of actual surface available for cells to grow on. Representative of prior art devices which increase the surface area internally of conventional roller bottles are U.S. Pat. Nos. 3,941,661 issued Mar. 2, 1976 and 4,317,886 issued Mar. 2, 1982.
Another approach to increasing the yield of cells developed internally of roller bottles includes the combination of increasing the surface area thereof, and the use of involved mechanical devices cooperating with these increased surfaces in order to remove a greater harvest of cells once they are developed on the increased surface internally of the bottles. Representative of these devices include those taught and claimed in U.S. Pat. Nos. 4,004,981 issued Jan. 25, 1977; 4,065,359 issued Dec. 27, 1977 and 4,600,694 issued July 15, 1986. While each of the above three patents have the effect of increasing the surface area internally of roller bottles and increasing the yield of cells removed therefrom, the internal devices utilized in these patents and the arrangements for scraping the cells from the increased surface areas are very involved and, increase the cost of roller bottles, and the product derived therefrom, substantially. Moreover, these are not single-use devices and have been used largely in the labs where they originated.
One arrangement, of course, utilized frequently in past procedures for removing cells from the internal surface of conventional roller bottles is simply the use of a scraper device in the form of a flat thin structure similar to a knife positioned at the end of a rod which a lab technician utilizes to manually scrape in a tedious manner the cells which have developed on the internal surface of a roller bottle.
An additional approach to cell removal is by other than mechanical means. Representative of these include U.S. Pat. No. 4,556,639 issued Dec. 3, 1985 which utilizes an inertial force in order to remove cells formed on the internal surface of bottles. U.S. Pat. No. 3,853,712 issued Dec. 10, 1984 uses the shearing action of fluid in order to remove cells or alternatively the use of an enzyme for removing cells. This patent teaches the combination of these two approaches, as well. A further approach includes that taught and claimed in U.S. Pat. No. 3,812,016 which teaches the use of sand or other granulate matter for physically removing the cells from the internal surface either alone or in combination with a shearing action from liquids.
With this invention, by contrast, an arrangement for mechanical removal of cells grown on the internal surface of roller bottles is provided with a device which may be folded so that it may be slipped through the neck of a conventional roller bottle. The folding of the device, in accordance herewith, is of flexible blades which, when they move past the neck of the roller bottle and into the bottle itself, spring back into their initial position so that the blades move against the internal surface of the roller bottle. Thereafter, the scraper blades are rotated, in accordance herewith, to scrape mechanically all of the cells which have formed on the internal surface of the roller bottle. In addition, the weight of the scraper and the differential rotation of the scraper and the bottle generates a functional force enhancing the scraping action.
With this arrangement, of course, the roller bottle itself does not need to be modified in any way in order to provide the scraping action in accordance herewith. As a consequence, the same roller bottles and roller apparatus is utilized without any expensive modifications.
An alternative embodiment of the device herein includes precise mechanical spreading of the blades of the scraper device prior to the placing of the roller bottle onto the roller apparatus. In this way, a more precise engagement of the internal surfaces of the roller bottle is provided with this embodiment.
Finally, an embodiment of the invention is provided which is the most simple and least expensive device provided in accordance with this invention. This embodiment includes the blades for engaging the internal surface in the same manner as discussed above with the previous embodiments, but this particular embodiment requires a roller bottle that has a removable top so that the fins or blades of the scraper apparatus may be inserted. This is the only modification and the scraper apparatus is extremely simple and inexpensive of construction.
Other objects and advantages of this invention will be apparent from the following description, the accompanying drawings and the appended claims.